6-4558976-T-C

Variant names:

• chr6-4558976-T-C
• rs84996
• ENST00000642310.1:n.313+22663A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642310.1(ENSG00000284823):​n.313+22663A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,060 control chromosomes in the GnomAD database, including 1,950 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (1950 hom., cov: 32)
• Consequence: ENSG00000284823 ENST00000642310.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 2 publications found

Genes affected

ENSG00000284823 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374894	XR_001743940.2	n.287+22663A>G		intron_variant	Intron 2 of 2
LOC105374894	XR_007059417.1	n.287+22663A>G		intron_variant	Intron 2 of 2
LOC105374894	XR_007059418.1	n.287+22663A>G		intron_variant	Intron 2 of 3
LOC105374894	XR_926409.3	n.287+22663A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284823	ENST00000642310.1	n.313+22663A>G		intron_variant	Intron 2 of 4
ENSG00000284823	ENST00000716074.1	n.886+22663A>G		intron_variant	Intron 4 of 4
ENSG00000284823	ENST00000827010.1	n.408+22663A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23894 AN: 151944 Hom.: 1949 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0784

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.181

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 23916 AN: 152060 Hom.: 1950 Cov.: 32 AF XY: 0.153 AC XY: 11381 AN XY: 74310

African (AFR) AF: 0.166 AC: 6900 AN: 41466

American (AMR) AF: 0.152 AC: 2321 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3468

East Asian (EAS) AF: 0.148 AC: 763 AN: 5162

South Asian (SAS) AF: 0.0793 AC: 381 AN: 4806

European-Finnish (FIN) AF: 0.122 AC: 1286 AN: 10582

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11016 AN: 67970

Other (OTH) AF: 0.181 AC: 382 AN: 2114

Alfa AF: 0.162 Hom.: 775

Bravo AF: 0.159

Asia WGS AF: 0.122 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.2
DANN	Benign	0.53
PhyloP100		-0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs84996; hg19: chr6-4559210;